The role of small leucine-rich proteoglycans in collagen fibrillogenesis

Kalamajski, Sebastian; Oldberg, Åke

doi:10.1016/j.matbio.2010.01.001

Cited by 386 publications

(345 citation statements)

References 53 publications

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“…Inhibition of TGF-b1/b3 in KAT-4/HT-29 downregulates the small-leucine rich repeat proteoglycan fibromodulin and the effects on carcinoma IFP and collagen fibrillar network recorded after TGF-b1/b3 inhibition is mimicked in KAT-4/HT-29 carcinomas grown in fibromodulin-deficient mice (8). Fibromodulin regulates collagen fibril assembly in dense connective tissues (41) and is upregulated and plays a pathogenic role in several models of fibrosis (8,(42)(43)(44). STI571 showed a trend to downregulate fibromodulin mRNA in KAT-4/HT-29 carcinoma but, due to a large variance, the changes did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 99%

The Tyrosine Kinase Inhibitor Imatinib Augments Extracellular Fluid Exchange and Reduces Average Collagen Fibril Diameter in Experimental Carcinoma

Olsson

Gustafsson

Zandt

et al. 2016

Molecular Cancer Therapeutics

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A typical obstacle to cancer therapy is the limited distribution of low molecular weight anticancer drugs within the carcinoma tissue. In experimental carcinoma, imatinib (STI571) increases efficacy of synchronized chemotherapy, reduces tumor interstitial fluid pressure, and increases interstitial fluid volume. STI571 also increases the water-perfusable fraction in metastases from human colorectal adenocarcinomas. Because the mechanism(s) behind these effects have not been fully elucidated, we investigated the hypothesis that STI571 alters specific properties of the stromal extracellular matrix. We analyzed STI571-treated human colorectal KAT-4/HT-29 experimental carcinomas, known to have a welldeveloped stromal compartment, for solute exchange and glycosaminoglycan content, as well as collagen content, structure, and synthesis. MRI of STI571-treated KAT-4/HT-29 experimental carcinomas showed a significantly increased efficacy in dynamic exchanges of solutes between tumor interstitium and blood. This effect was paralleled by a distinct change of the stromal collagen network architecture, manifested by a decreased average collagen fibril diameter, and increased collagen turnover. The glycosaminoglycan content was unchanged. Furthermore, the apparent effects on the stromal cellular composition were limited to a reduction in an NG2-positive stromal cell population. The current data support the hypothesis that the collagen network architecture influences the dynamic exchanges of solutes between blood and carcinoma tissue. It is conceivable that STI571 reprograms distinct nonvascular stromal cells to produce a looser extracellular matrix, ultimately improving transport characteristics for traditional chemotherapeutic agents. Mol Cancer Ther; 15(10); 2455-64. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

The Tyrosine Kinase Inhibitor Imatinib Augments Extracellular Fluid Exchange and Reduces Average Collagen Fibril Diameter in Experimental Carcinoma

Olsson

Gustafsson

Zandt

et al. 2016

Molecular Cancer Therapeutics

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“…This would suggest a protective role of lumican during heart failure progression of pressureoverloaded hearts, and in our group, we are currently testing this hypothesis by subjecting lumican KO mice 123 to AB (unpublished results and ongoing work). 223 In Paper III, increased formation of the dimeric and cross-linked form of collagen I was observed after stimulation with lumican, possibly due to increased activity of LOX. This finding suggests that lumican increases collagen cross-linking, ultimately leading to reduced turnover of collagens and a stiffer heart.…”

Section: The Multiple Roles Of Syndecan-4 In Cardiac Remodelingmentioning

confidence: 90%

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

et al. 2013

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Sustained pressure overload induces heart failure, the main cause of mortality in the Western world. Increased understanding of the underlying molecular mechanisms is essential to improve heart failure treatment. Despite important functions in other tissues, cardiac proteoglycans have received little attention. Syndecan‐4, a transmembrane heparan sulfate proteoglycan, is essential for pathological remodeling, and we here investigated its expression and shedding during heart failure. Pressure overload induced by aortic banding for 24 h and 1 week in mice increased syndecan‐4 mRNA, which correlated with mRNA of inflammatory cytokines. In cardiac myocytes and fibroblasts, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide through the toll‐like receptor‐4, induced syndecan‐4 mRNA. Bioinformatical and mutational analyses in HEK293 cells identified a functional site for the proinflammatory nuclear factor‐κB transcription factor in the syndecan‐4 promoter, and nuclear factor‐κB regulated syndecan‐4 mRNA in cardiac cells. Interestingly, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide induced nuclear factor‐κB‐dependent shedding of the syndecan‐4 ectodomain from cardiac cells. Overexpression of syndecan‐4 with mutated enzyme‐interacting domains suggested enzyme‐dependent heparan sulfate chains to regulate shedding. In cardiac fibroblasts, lipopolysaccharide reduced focal adhesion assembly, shown by immunohistochemistry, suggesting that inflammation‐induced shedding affects function. After aortic banding, a time‐dependent cardiac recruitment of T lymphocytes was observed by measuring CD3, CD4 and CD8 mRNA, which was reduced in syndecan‐4 knockout hearts. Finally, syndecan‐4 mRNA and shedding were upregulated in failing human hearts. Conclusively, our data suggest that syndecan‐4 plays an important role in the immune response of the heart to increased pressure, influencing cardiac remodeling and failure progression.

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“…It is well established that SLRPs play a role in the stabilization and assembly of collagens and elastic fibers. 32,33 Thus, for many years, SLRPs were considered to be merely static props of the ECM. The finding that decorin, besides being a structural matrix component, acts as a signaling molecule gave rise to a new paradigm of how SLRPs regulate a host of biologic processes, such as differentiation, proliferation, migration and apoptosis.…”

Section: The Family Of Small Leucine-rich Proteoglycansmentioning

confidence: 99%

Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

2012

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The role of small leucine-rich proteoglycans in collagen fibrillogenesis

Cited by 386 publications

References 53 publications

The Tyrosine Kinase Inhibitor Imatinib Augments Extracellular Fluid Exchange and Reduces Average Collagen Fibril Diameter in Experimental Carcinoma

The Tyrosine Kinase Inhibitor Imatinib Augments Extracellular Fluid Exchange and Reduces Average Collagen Fibril Diameter in Experimental Carcinoma

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

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